Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: Results from a multicenter, international, randomized, placebo-controlled, dose-selection study

Søren Fast, Laszlo Hegedüs, Furio Pacini, Aldo Pinchera, Angela M. Leung, Mario Vaisman, Christoph Reiners, Jean Louis Wemeau, Dyde A. Huysmans, William Harper, Irina Rachinsky, Hevelyn Noemberg De Souza, Maria G. Castagna, Lucia Antonangeli, Lewis E. Braverman, Rossana Corbo, Christian Düren, Emmanuelle Proust-Lemoine, Christopher Marriott, Albert DriedgerPeter Grupe, Torquil Watt, James Magner, Annie Purvis, Hans Graf

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine (131I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with 131I therapy. Methods: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2±9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0mL; range 31.9-242.2mL) were randomized to receive placebo (n=32), 0.01mg MRrhTSH (n=30), or 0.03mg MRrhTSH (n=33) 24 hours before a calculated 131I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. Results: At six months, TV reduction was enhanced in the 0.03mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44±12.7% (SD) in the placebo group, 41±21.0% in the 0.01mg MRrhTSH group, and 53±18.6% in the 0.03mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03mg MRrhTSH group, the subset of patients with basal 131I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03mg MRrhTSH group (13.4±23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01mg, and 0.03mg MRrhTSH groups respectively. The overall safety profile of the study was favorable. Conclusions: When used as adjuvant to 131I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤0.03mg, indicating that the lower threshold for efficacy is around this level.

Original languageEnglish
Pages (from-to)727-735
Number of pages9
JournalThyroid
Volume24
Issue number4
DOIs
StatePublished - 1 Apr 2014
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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